DESCRIPTION: This proposal investigates the molecular mechanisms of K selectivity and inward rectification in IRK channels expressed in Xenopus oocytes. In particular, the investigator will investigate the selectivity of the K binding site using selective IRK channel mutants, and rectification that results from intracellular blocking ions. The ROMK1 and IRK1 channels are appropriate channels on which to carry out these investigations. The mutant channels that conduct fall into two categories: those that have ion selectivity like WT channel and those that are nonselective. The proposal investigates the mechanisms rectification and the interactions of specific polyamines with rectifying channels.